AN OVERVIEW OF MOLECULAR DOCKING: PRINCIPLE, AND ITS APPLICATION IN DRUG DISCOVERY

Abstract

Structure-based drug discovery utilises molecular docking as a computational tool to forecast the optimal binding conformation and affinity of specific ligands within the active site. Virtual screening, lead optimisation, and rational design of novel therapeutic agents are facilitated by this technique through the use of molecular recognition processes. Molecular docking is based on the principle of searching for suitable ligand orientations and conformations within the binding pocket using search algorithms, and then scoring functions are used to evaluate these poses in order to estimate binding energies derived from intermolecular interactions. The use of molecular docking in drug discovery is highly beneficial, particularly in structure-activity relationship studies, polypharmacology assessments, and pharmacophore modelling, but it presents challenges such as restricted receptor flexibility modelling and simplified treatment of solvent effects. These limitations are being increasingly addressed by the continuous evolution of computational methodologies, scoring functions, and integration with machine learning. This article provides a comprehensive overview of the molecular docking process, its underlying principles, and its broad applications in modern drug discovery pipelines.